What’s The Damage?

A graphic presentation of the damage-response framework from Casadevall, A. & Pirofski, L. A.  Nature Rev. Microbiol.   1 , 17–24 (2003).

A graphic presentation of the damage-response framework from Casadevall, A. & Pirofski, L. A. Nature Rev. Microbiol. 1, 17–24 (2003).

In the realm of infectious disease we often talk of microbes invading our bodies and a war being sparked. In this war our immune system, often aided by antimicrobial therapy, attempts to quell the infection by eradicating the pathogen. However, it has become increasingly clear that it isn't just any microbe or every instance of microbial contact with our body that merits war and antimicrobial therapy. A microbe, depending on the context, may not be acting in the role of pathogen. Understanding this concept is important for a whole host of reasons including good antimicrobial stewardship, minimizing damage to the microbiome, and perusing novel avenues of treatment and diagnosis.

So what is the key to knowing when a microbe merits concern and is not just in a colonizer or commensal role? According to Drs. Arturo Casadevall and Liise-anne Pirofski’s (who delivered the prestigious Maxwell Finland Lecture on this topic last year) path-breaking commentary in Nature: damage. Damage can be the result of the microbe, the immune system’s response to the microbe, or a combination of the two. As they write, “Disease is one of several possible outcomes of an interaction between a host and a microbe.”

What their “damage-response” framework does is integrate much research into an actionable principle that can be employed when thinking of not only how best to treat (or not) a specific patient but what types of treatments should be developed.

Traditionally, the focus of treatment has almost exclusively been on developing therapies such as vaccines, antibiotics, antifungals, and antivirals which target the microbe. But, realizing that disease is an interaction—and not a one-way process—opens up numerous approaches to infectious disease treatment that affect the other aspect of disease: the host’s immune response.

Modulating the immune response, or immunomodulation, is something that has been used for select infectious diseases such as Pneumocystis pneumonia and Tuberculous meningitis for some time. In recent years, there has been an interest in using other immunomodulating compounds, such as statins and antibiotics that possess additional immunomodulating properties, for myriad infectious diseases from influenza to sepsis. In this vein, a recent paper described the benefit of corticosteroid use in the treatment of pneumonia. Diagnostic testing will also benefit from this perspective as host-side markers of disease will be used to supplement traditional microbiological tests that often produce delayed results.

As the march of antibiotic resistance continues, understanding how to use immunomodulation will take on growing importance as traditional approaches to disease will increasingly be rendered ineffectual. Additionally, and more important, several infectious diseases that still confer a high degree of morbidity and mortality—despite microbiological eradication through antimicrobials—will benefit from the incorporation of this paradigm into treatment and diagnosis. Casadevall and Pirofski, by conceptualizing an integrated and comprehensive approach to infectious disease, have provided a tool from which much progress can spring.